PMID- 15256805
OWN - NLM
STAT- MEDLINE
DCOM- 20041216
LR  - 20190610
IS  - 0250-8095 (Print)
IS  - 0250-8095 (Linking)
VI  - 24
IP  - 4
DP  - 2004 Jul-Aug
TI  - Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle 
      cells.
PG  - 387-92
AB  - BACKGROUND/AIMS: IL-6, an inducer of the acute-phase response, is linked with the 
      development of vascular disease and atherosclerosis. One mechanism likely 
      involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 
      can induce VSMC proliferation and the release of monocyte chemoattractant 
      protein-1 (MCP-1). We hypothesized that this stimulation occurs via the JAK 
      (janus-activated kinase)/STAT (signal and transducers and activators of 
      transcription) signaling pathway. METHODS: Rat VSMC were stimulated with IL-6 in 
      the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by 
      Western), MCP-1 (by ELISA) and DNA synthesis (by (3)H-thymidine incorporation) 
      was determined. RESULTS: IL-6 rapidly induced phosphorylation of STAT 3 in a 
      dose- and time-dependent manner with a peak expression at 30 min. IL-6 also 
      stimulated MCP-1 protein production and DNA synthesis dose dependently. 50 microM 
      of AG490, a specific JAK 2 inhibitor, partially inhibited STAT 3 activation and 
      MCP-1 production, with near complete inhibition of DNA synthesis. CONCLUSION: The 
      JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA 
      synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in 
      the development of vascular disease and atherosclerosis.
FAU - Watanabe, Susumu
AU  - Watanabe S
AD  - Baylor College of Medicine, Houston, Tex., USA. 
      susumuw@showa-university-fujigaoka.gr.jp
FAU - Mu, Wei
AU  - Mu W
FAU - Kahn, Andrew
AU  - Kahn A
FAU - Jing, Naijie
AU  - Jing N
FAU - Li, Jin H
AU  - Li JH
FAU - Lan, Hui Y
AU  - Lan HY
FAU - Nakagawa, Takahiko
AU  - Nakagawa T
FAU - Ohashi, Ryuji
AU  - Ohashi R
FAU - Johnson, Richard J
AU  - Johnson RJ
LA  - eng
GR  - I01 BX002586/BX/BLRD VA/United States
GR  - DK-52121/DK/NIDDK NIH HHS/United States
GR  - DK-64233/DK/NIDDK NIH HHS/United States
GR  - HL-68607/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040709
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - 0 (Trans-Activators)
RN  - 0 (Tyrphostins)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak2 protein, rat)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Arteriosclerosis/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - DNA/biosynthesis
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Interleukin-6/*pharmacology
MH  - Janus Kinase 2
MH  - Muscle, Smooth, Vascular/cytology/drug effects/*enzymology
MH  - Phosphorylation/drug effects
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Rats
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/drug effects/*physiology
MH  - Trans-Activators/*metabolism
MH  - Tyrphostins/pharmacology
EDAT- 2004/07/17 05:00
MHDA- 2004/12/17 09:00
CRDT- 2004/07/17 05:00
PHST- 2004/03/30 00:00 [received]
PHST- 2004/06/01 00:00 [accepted]
PHST- 2004/07/17 05:00 [pubmed]
PHST- 2004/12/17 09:00 [medline]
PHST- 2004/07/17 05:00 [entrez]
AID - 79706 [pii]
AID - 10.1159/000079706 [doi]
PST - ppublish
SO  - Am J Nephrol. 2004 Jul-Aug;24(4):387-92. doi: 10.1159/000079706. Epub 2004 Jul 9.